THe purpose of this project is to examine the subcellular and extracellular structure of nerve and muscle and relate such structure to function. Electron microscopy in TEM, STEM and analytical electron beam probe modes, such as EELS and EDAX, determination of proteins contributing to these structures and structural modeling are methods used in this study. The following structures are probed: l) Neuroplasmic lattice, 2) neurofilaments, 3) microtubules, 4) axolemma, 5) glial cell membranes, and 6) myofilaments. Methods developed and used in this study are: l) Stereoscopic imaging, 2) optical autocorrelation, 3) fast Fourier transformation (FFT) of STEM video images, and 4) STEM video image filtering and image enhancement using reverse Fourier transformation. Video imaged light microscopy is used to study living neurons in dark field or differential interference contrast. In diffusion experiments using whole squid giant axons, the combined application of EM and EDAX has shown that ferritin molecules (about ll0A diameter) penetrate the sheath complex (including the basement lamella) only after trypsin treatment, but not the intercellular spaces between Schwann cells, their cytoplasm, or the axoplasm. Good correlation has been achieved between the EM fine structure of axoplasm and the effluent and residual proteins (as determined by SDS-PAGE) in "chemical dissection" experiments involving extraction with physiological buffer, activation of a resident protease specific for neurofilaments, and trypsin treatment, which cleaves microtubule associated protein (MAP) cross-bridges between neurotubules. Video-enhanced DIC microscopy (VEDIC), in conjunction with electron microscopy of squid and lobster axons, suggest a close linkage of fast axonal transport (FAT) with the neurotubular component of the neuroplasmic lattice. Preliminary VEDIC observations indicate the feasibility of developing a glycerol/DMSO model system for FAT using squid axons.